Ether phospholipids (phospholipids with ether linkage in first glycerol position) are synthesized in peroxisomes and microsomes and contribute to signal transduction and membrane structure. Their brain metabolism, which has not been correctly quantified, is disturbed in Zellweger's syndrome and adenoleukodystrophy, human neurodevelopmental disorders. Intravenously injected [1,1-3H]hexadecanol was incorporated into brain ether phospholipids of unanesethetized awake rats, more so (97%) into gray than white matter. A mathematical model was elaborated to interpret the data. It showed that synthesis half-lives of different microsomal ether phospholipids lipids were 15-30 minutes, compared with erroneous reported half-lives of days to weeks. This mathematical model is being used to quantify brain ether phospholipid metabolism in a mouse model of human peroxisomal disease, in which the gene for the peroxisomal proliferator-activated receptor b (d) (PPARb) is disrupted. Marked abnormalities in brain lipid content were found in this model.